The synthesis and biological evaluation (in vivo and in vitro) of the highly active 3-azabicyclo(3.3.1)nonane diastereoisomers will be undertaken to develop a new concept on the molecular mode of action and interaction of narcotic antagonists with their receptors. The new concept is based upon composite superstructures and stereochemical superimposability patterns and can be proven by linear free energy correlation of the biological data from the two series of 3-azabicyclo(3.3.1)nonane diastereoisomers. X-ray crystallographic studies are contemplated in order to more closely define the spatial relationships of the pharmacophoric units in these and related molecules. These studies should lead to refinement of a composite superstructure of general utility as a model for the design and ultimate synthesis, testing and exploitation of the new prototypes. Biological testing (hot plate and rat brain homogenate stereospecific inhibition of binding of tritiated naloxone) will be undertaken at NIDA.